Adjuvants targeting innate and adaptive immunity synergize to enhance tumor immunotherapy.
Because of mechanisms of self-tolerance, many tumor-specific CD8 T cells exhibit low avidity for tumor antigens and would benefit from strategies that enhance their numbers and effector function. Here we demonstrate that the combined use of two different types of immune adjuvants, one that directly targets the CD8 cell, IL-2/anti-IL-2 mAb complexes, and one that targets the innate immune system, poly(I:C), can achieve this goal. Provision of IL-2/mAb complexes was found to enhance the activation and effector function of low-avidity tumor-specific T cells, yet this was insufficient to achieve tumor eradication. The addition of poly(I:C) further increased the accumulation of granzyme B-expressing effectors within the tumor and resulted in tumor eradication. This strategy presents many of the benefits of whole-body irradiation, including the provision of high levels of homeostatic cytokines, enhanced expansion of effector cells relative to regulatory T cells, and provision of inflammatory cytokines, and is therefore likely to serve as a strategy for both tumor vaccines and adoptive immunotherapy of cancer.
Verdeil
Grégory
G
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Marquardt
Kristi
K
Surh
Charles D
CD
Sherman
Linda A
LA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000737:chemistry; D016207:Cytokines; D007109:Immunity / Q000187:drug effects*; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000628:therapy*; D011070:Poly I-C / Q000627:therapeutic use; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D016207:Cytokines; D007376:Interleukin-2; D011070:Poly I-C